PPAR and PPAR as Modulators of Neoplasia and Cell Fate
Figure 1
Pax8PPAR and mammary cell fate determination. Pax8PPAR acts in a dominant-negative fashion to block PPAR-dependent transactivation and upregulation of PTEN. MMTV-Pax8PPAR mice exhibit reduced PTEN and activation of Ras and ERK, presumably through activation of PI3K (p85 and p110). ERK activates ER transcriptionally and posttranslationally, and Pax8PPAR may interfere with the ability of PPAR to inhibit ER transactivation. Mammary epithelial cells isolated from the mammary glands of MMTV-Pax8PPAR mice contain a higher percentage of CD24+/CD29hi stem/progenitor cells, and present with predominantly ER+ ductal carcinomas following carcinogenesis, suggesting a role of PPAR in cell fate determination.
